1. Field of the Invention
The present invention relates to compounds for the treatment of immune-related diseases, in particular to cyclohexenone compounds isolated and purified from Antrodia camphorata extracts and can be applied in treatment of autoimmune immune diseases such as systemic lupus erythematosus (SLE).
2. The Prior Arts
There are many types of autoimmune diseases result from an aberrant immune response of the body and cause self-destructive. Prominent examples' include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), Scleroderma, Polymyositis, dermatomyositis, Anaphylactoid purpura, Sjögren's syndrome and the like. Others such as primary biliary cirrhosis (PBC), chronic active hepatitis, and Hashimoto's thyroiditis, are all related to autoimmune diseases. Among them, systemic lupus erythematosus (SLE) is the most serious disease, which is common in women of child-bearing age. SLE patients produce autoantibodies called antinuclear antibodies (ANA) targeted against autoantigens inside cell nucleus. These autoantibodies can cause multiple damages in tissues and organs such as skin, joint, skeleton, kidney, cardiovascular system, agglutination system, intestines and stomach, serous membrane (pericardium, pleura, and peritoneum), neural system and the like. Some of the antibodies form immune complexes when bind with antigens, which can be deposited in cells of different tissues during circulation. Clinical manifestations include butterfly rashes, hemolytic anemia, arthritis, blood vessel inflammation, nephritis and so on. A standard treatment for autoimmune diseases is administration of steroids or other chemical drugs. However, patients on long term treatment exhibited uncomfortable complication or side effects. Therefore, it will be beneficial to the patients if natural and side effect free traditional Chinese herb medicines are used to treat autoimmune diseases.
Antrodia camphorata is also called Chang-Zhi, Niu Chang-Zhi, red camphor mushroom and so on, which is a perennial mushroom belonging to the order Aphyllophorales, the family Polyporaceae. It is an endemic species in Taiwan growing on the inner rotten heart wood wall of Cinnamomum kanehirae Hay. Cinnamoum kanehirai Hay is rarely distributed and being overcut unlawfully, which makes Antrodia camphorata growing inside the tree in the wild became even rare. The price of Antrodia camphorata is very expensive due to the extremely slow growth rate of natural Antrodia camphorata that only grows between June to October.
The fruiting bodies of Antrodia camphorata are perennial, sessile, hard and woody, which exhales strong smell of sassafras (camphor aroma). The appearances are various with plate-like, bell-like, hoof-like, or tower-like shapes. They are reddish in color and flat when young, attached to the surface of wood. Then the brims of the front end become little curled tilted and extend to the surroundings. The color turns to be faded red-brown or cream yellow brown, with ostioles all over. It has very high medical value in this stage.
In traditional Taiwanese medicine, Antrodia camphorata is commonly used as an antidotal, liver protective, anti-cancer drug. Antrodia camphorata, like general edible and medicinal mushrooms, is rich in numerous nutrients including polysaccharides (such as β-glucosan), triterpenoids, superoxide dismutase (SOD), adenosine, proteins (immunoglobulins), vitamins (such as vitamin B, nicotinic acid), trace elements (such as calcium, phosphorus and germanium and so on), nucleic acid, agglutinin, amino acids, steroids, lignins and stabilizers for blood pressure (such as antodia acid) and the like. These physiologically active ingredients are believed to exhibit effects such as: anti-tumor activities, increasing immuno-modulating activities, anti-allergy, anti-bacteria, anti-high blood pressure, decreasing blood sugar, decreasing cholesterol and the like.
Triterpenoids are the most studied component among the numerous compositions of Antrodia camphorata. Triterpenoids are the summary terms for natural compounds, which contain 30 carbon atoms with the pentacyclic or hexacyclic structures. The bitter taste of Antrodia camphorata is from the component of triterpenoids. Three novel ergostane-type triterpenoids (antcin A, antcin B, antcin C) were isolated by Cherng et al. from the fruiting bodies of Antrodia camphorata (Cherng, I. H., and Chiang, H. C. 1995. Three new triterpenoids from Antrodia cinnamomea. J. Nat. Prod. 58: 365-371). Three new compounds zhankuic acid A, zhankuic acid B and zhankuic acid were extracted from the fruiting bodies of Antrodia camphorata with ethanol by Chen et al. (Chen, C. H., and Yang, S. W. 1995. New steroid acids from Antrodia cinnamomea,—a fungus parasitic on Cinnamomum micranthum. J. Nat. Prod. 58: 1655-1661). In addition, Chemg et al. also found three other new triterpenoids from the fruiting bodies of Antrodia camphorata, which are sesquiterpene lactone and 2 biphenyl derived compounds, 4,7-dimethoxy-5-methyl-1,3-benzodioxole and 2,2′,5,5′-teramethoxy-3,4,3′,4′-bi-methylenedioxy-6,6′-dimethylbiphenyl (Chiang, H. C., Wu, D. P., Cherng, I. W., and Ueng, C. H.1995. A sesquiterpene lactone, phenyl and biphenyl compounds from Antrodia cinnamomea. Phytochemistry. 39: 613-616). In 1996, four novel ergostane-type triterpenoids (antcins E and F and methyl antcinates G and H) were isolated by Chemg et al. with the same analytic methods (Chemg, I. H., Wu, D. P., and Chiang, H. C. 1996. Triteroenoids from Antrodia cinnamomea. Phytochemistry. 41: 263-267). And two ergostane related steroids, zhankuic acids D and E together with three lanosta related triterpenes, 15 alpha-acetyl-dehydrosulphurenic acid, dehydroeburicoic acid, dehydrosulphurenic acid were isolated by Yang et al. (Yang, S. W., Shen, Y. C., and Chen, C. H.1996. Steroids and triterpenoids of Antrodia cinnamomea—a fungus parasitic on Cinnamomum micranthum. Phytochemistry. 41: 1389-1392).
Antrodia camphorata extracts were reported to have the abovementioned effects from the previous experiments, and the components were analyzed in succession. However, the potential use of Antrodia camphorata extracts in treatment of autoimmune diseases has never been reported. Further experiments are needed to identify the effective composition to help treat autoimmune conditions. The natural components of Antrodia camphorata extracts will greatly contributes great beneficial effects in preventing or treating systemic lupus erythematosus if the real effective composition is found. In addition, this will help to prevent the side effects or complication caused by chemical pharmaceutical drugs such as steroids in treating autoimmune disease.